It is known that in the chemistry of liquid/liquid phase reactions, the fundamental requirement for a bimolecular reaction to occur is collision, and that no amount of kinetic energy contained by one species can make it react with another if the reactants do not come into proximity. In the past, the problem of phase separation has traditionally been overcome by utilizing certain solvents, such as a dipolar aprotic solvent which provides mutual dissolution of both inorganic salts and organic substrates; however, the principle difficulty with this approach has been that the solvents are often costly, difficult to recover after completion of the reaction and hard to purify, dry and maintain in the required anhydrous state. An alternative to such a procedure involving specialized solvents, is the use of phase transfer catalysts such as quaternary phosphonium and ammonium halides to provide the desired two phase solubility and anion exchange with the inorganic species in the aqueous phase. Specifically in this catalysis, the aqueous phase, which contains the inorganic salt reservoir as a base or nucleophile, is contacted with the organic phase containing the organic substrate to be reacted with the salt through anion exchange of the inorganic salt with the quaternary catalyst and formation of a quaternary nucleophile soluble in the organic phase. The quaternized salt catalysts of the prior art have been highly effective in solvation by ion pair extraction of the OH.sup.- anion of the inorganic salt leading to formation of a dihalo carbene radical suitable for reaction with the organic coreactant. Obviously, in these reactions, the degree and/or rate at which the anion can be transferred into the organic phase is a most important factor. It has now been found that certain novel quarternary ammonium and phosphonium catalysts provide a more complete and/or rapid transfer of hydroxide or other anions to the reaction zone affording higher yields and shorter reaction times thereby enhancing the economy of the chemical process.
Accordingly, it is an object of this invention to provide a more efficient and effective phase transfer reaction with an improved catalyst.
A second object of the invention is to provide a more economical and commercially feasible process for effecting phase transfer reactions involving olefinically unsaturated compounds through the formation of a dihalo carbene.
These and other objects of the invention will become apparent from the following description and disclosure.
According to this invention, phase transfer reactions including cyclopropanation, substitution nucleophilic bimolecular displacement (S.sub.n 2) and addition reactions are catalyzed with a polyoxyalkylene quaternized salt having the formula: ##STR2## wherein R is alkyl of 8 to 30 carbon atoms, blends thereof or alkyl-substituted phenyl of 10 to 24 carbon atoms;
n has a value of from 2 to 14 and includes mixtures within that range; PA0 R.sub.1 and R.sub.2 are hydrogen atoms or one of R.sub.1 and R.sub.2 is methyl; PA0 R.sub.3, R.sub.4 and R.sub.5 are independently hydrogen, an alkyl radical of 1 to 6 carbon atoms or phenyl or one of R.sub.3, R.sub.4 and R.sub.5 is an alkylene-alkali metal sulfonate; PA0 A is a phosphorous or a nitrogen atom; and PA0 halo is a chlorine or bromine ion.
The improvements obtained with the present quaternized salt is mainly due to the polyether moiety which reduces the interfacial tension, thus affording a kinetic enhancement of ion-pair phase transfer. Because of the greater water affinity of the polyether moiety, as compared to the corresponding hydrocarbon, the present anion exchanged quaternary compound remains in or near the water/organic interface to provide a more rapid and complete transfer of the inorganic nucleophile and subsequent formation of the dihalo carbene required for contact with the organic coreactant in cyclopropanation reactions.
Because the polyether moiety of the present quaternary catalyst has an affinity for the water phase, the catalyst molecule affords surfactant properties, i.e. reducing interfacial tension, increasing the rate of replicate exchange and transfer of anion (micellar extraction) to the organic phase, thereby providing a higher rate of reactive intermediate generation; e.g. trichloromethyl anion generation.
In the present reactions, the aqueous inorganic salt reservoir contains the OH.sup.- nucleophile supplied by an alkali or alkaline earth metal hydroxide and it is this nucleophile which must be contacted with the organic phase substrate for the essential generation of carbene or naked, trihalomethyl anion, which in turn reacts, by 1,2- or 1,4- addition, or S.sub.n 2 displacement mechanisms, with the normally liquid, olefinically unsaturated coreactant dissolved in the organic substrate employed as the organic phase.
The cyclopropanation catalysis of the present process is illustrated by the following equations wherein sodium hydroxide is selected as the water soluble inorganic salt; chloroform is selected as the organic substrate, ethylene is the organic coreactant and a quarternary chloride (Q.sup.+ Cl.sup.-) represents the quarternized catalyst. ##STR3##
When the unsaturated organic coreactant contains a carbonyl group, eg. methyl acrylate, the reaction in the organic phase proceeds mainly by the following 1,4 Michael addition ##STR4##
As shown in the above mechanistic representation the initial anion exchange takes place in the aqueous phase, preferentially at the interface, to provide a soluble quaternized hydroxy nucleophile which partitions into both organic and aqueous phases through the surfactant modified interface. The quaternary hydroxide nucleophile activated by solubilization in the organic phase deprotonates the solvent and exchanges anions with the organic substrate at the interface by acid/base deprotonation, to form the trihalomethyl anion which in turn dissociates to produce the corresponding dihalocarbene radical or reacts by addition to the olefinic carbonyl compound followed by protonation. The original hydrophilic quaternary halide is reformed as a by-product and enters the aqueous phase for further anion exchange. In the reaction with a hydrocarbon olefin, the dihalocarbene reacts with the olefin coreactant in the organic phase to provide the desired cyclopropanation product of the process. The above equations are intended only to illustrate a mechanism for the rate enhanced phase transfer reactions of th is invention and are not to be construed as limiting the scope of this invention which is broadly applicable to all rate limited liquid/liquid phase transfer of reaction intermediates.
According to this invention the aqueous phase comprises an inorganic salt capable of generating a hydroxy anion. Although sodium and potassium hydroxides are most preferred, it is to be understood that other inorganic hydroxides, such as any alkali metal or alkaline earth metal hydroxide, can also be used. The inorganic salt is generally maintained in the aqueous phase at a concentration of between about 5% and about 60%, preferably between about 25% and about 50%, and the volume ratio of aqueous phase to organic phase is broadly between about 1:1 and about 1:3, more desirably between about 1:2 and about 1:3.
The preferred quaternary ammonium catalysts of the present invention are those in which R is alkyl containing from 8 to 18 carbon atoms or an alkyl substituted phenyl radical wherein said alkyl substituent contains from 4 to 10 carbon atoms and may occupy 1 or 2 positions on the phenyl ring; A is a nitrogen atom; halo.sup.- is a chloride anion and R.sub.3, R.sub.4 and R.sub.5 are independently alkyl of 1 or 2 carbon atoms or phenyl or one of R.sub.3, R.sub.4 and R.sub.5 is hydrogen and/or .beta.-sulfoethyl sodium salt. The quaternary salt catalysts are easily and conventionally prepared by reacting the corresponding polyoxyalkylene monochloride with the corresponding primary, secondary or tertiary amine or phosphine for a period of 6 to 20 hours at a temperature of between about 100.degree. C. and about 160.degree. C. under a pressure of from about 14 to about 60 psig. The reaction proceeds by S.sub.n 2 displacement as illustrated by the equation: ##STR5## wherein Br.sup.- can be substituted for Cl.sup.- in an identical reaction. The reaction may be carried out in aqueous solution wherein the amine or phosphine is present in a concentration of between about 10 to about 35% in an inert solvent such as water, isopropanol, or other inert solvent. A more detailed discussion for the preparation of the present quarternized catalyst compounds is found in copending patent application Ser. No. 096,991, filed Nov. 23, 1979 on Quarternary Drivatives of Polyoxy Alkylenes and also in U.S. Pat. No. 2,745,877; U.S. Pat. No. 3,404,183 and The Journal of the American Chemical Society, Volume 93, page 195, 1971.
The concentration of the quarternary catalysts in the initial aqueous phase is maintained between the critical micell concentration and 1%, preferably between about 0.1 and about 0.5%; as is consistent with a mole ratio of from about 0.0001:1 to about 0.01:1, preferably from about 0.0003:1 to about 0.0015:1, of quarternized catalyst with respect to organic substrate in the system.
Organic substrates which are suitably employed in the present phase transfer reactions are the iodides, chlorides or bromides of methane and mixed halogenated methanes, preferably a normally liquid halogenated methane, which are capable of generating a carbene intermediate. Specific examples of such substrates include chloroform, bromoform, iodoform, dichloromethane, and combinations of these. The substrate is present as a carrier for the olefinically unsaturated reactant in the organic phase and is present in a mole ratio of between about 5:1 and 20:1, preferably 10:1 and 15:1, with respect to said olefinically unsaturated coreactant.
The olefinically unsaturated coreactant of the present process includes any of the electron rich substances containing olefinic unsaturation either, as an aliphatic or cycloaliphatic olefin or as an olefinic group, or as a side chain. Specific examples of such olefinic substances include styrene, cyclohexene, phenylpropene, indene, thiophene, methyl acrylate, methyl methacrylate, 1-octene, 1-hexene, 1,4-dichlorobutene-2, isobutene-2, conjugated dienes such as 1,3-butadiene, 2,4,6-cyclooctatriene, cyclopentadiene, vinylbenzenes, and any of those olefins designated on pages 23 through 42 of PHASE TRANSFER CATALYSIS IN ORGANIC SYNTHESIS, Volume 4 by W. P. Weber and G. W. Gokel, Springer-Verlag., 1977 and in the addition reactions and substitution reactions illustrated therein on pages 49 through 56. The present phase transfer reactions also include deuterium phase reactions discussed in Phase Transfer Catalysis by C. M. Starks and C. Liotta, Academic Press, 1978, pages 341-343.
The reactions of the present invention are carried out under relatively mild conditions including a temperature of between about 20.degree. and about 100.degree. C. preferably between about 25.degree. and about 75.degree. C.; under a pressure of about 14 psig. to about 50 psig.; more desirably, from about 14 psig. to about 25 psig. for a period of from about 0.5 to about 12 hours, more often between about 1 and about 6 hours.